Research Article

A central master driver of psychosocial stress responses in the rat

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Science  06 Mar 2020:
Vol. 367, Issue 6482, pp. 1105-1112
DOI: 10.1126/science.aaz4639

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A major psychosocial stress circuit

Psychological stress induces various physiological responses by activating the sympathetic nervous system. The brain circuits involved in these functions are still not completely understood. In a rat model, Kataoka et al. combined anatomical tracing, immediate early gene expression analysis, pharmacology, optogenetics, electrophysiology, and genetic cell ablation to provide evidence for the prominent role of a ventral part of the medial prefrontal cortex in sympathetic responses to social defeat stress. This brain region sends excitatory projections to the dorsomedial hypothalamus as a central coordinator of the psychosocial stress responses. This pathway is crucial for understanding how psychosocial stress influences a variety of body functions.

Science, this issue p. 1105


The mechanism by which psychological stress elicits various physiological responses is unknown. We discovered a central master neural pathway in rats that drives autonomic and behavioral stress responses by connecting the corticolimbic stress circuits to the hypothalamus. Psychosocial stress signals from emotion-related forebrain regions activated a VGLUT1-positive glutamatergic pathway from the dorsal peduncular cortex and dorsal tenia tecta (DP/DTT), an unexplored prefrontal cortical area, to the dorsomedial hypothalamus (DMH), a hypothalamic autonomic center. Genetic ablation and optogenetics revealed that the DP/DTT→DMH pathway drives thermogenic, hyperthermic, and cardiovascular sympathetic responses to psychosocial stress without contributing to basal homeostasis. This pathway also mediates avoidance behavior from psychosocial stressors. Given the variety of stress responses driven by the DP/DTT→DMH pathway, the DP/DTT can be a potential target for treating psychosomatic disorders.

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